Up-regulation of the kidney renin angiotensin system contributes to long-term renal dysfunction in severe food restricted-refed female rats

Background: Severe food restriction (sFR) due to various psychological, environmental, and economical reasons can have adverse consequences to cardiovascular functioning and health. Less understood are the long-term risks for developing cardiovascular disease after the sFR period has ended. The renin-angiotensin system (RAS) is responsible for regulating blood pressure and we have found that the RAS is chronically upregulated months after the sFR is over and body weight (BW) recovered due to refeeding (sFR-Refed). AIM: Determine the role of the kidney in the chronic up-regulation of the RAS in sFR-Refed rats. Methods: We investigated the long-term consequences of sFR after refeeding on kidney structure and function in sFR-Refed rats. Female Fischer rats (3-months-old) were maintained on normal chow (Ctrl) ad libitum or a 60% caloric restricted diet for 2 weeks. Thereafter, all rats received regular chow ad libitum for 3 months. Kidney function was analyzed by precision ultrasound. ACE expression (qPCR) and activity (fluorescent assay) were measured and renal pathology was assessed by H&E staining. Results: After 2 weeks of sFR, rats lost 15% of their initial BW [DFinal/Initial): Ctrl, 1.50±0.80 vs sFR, -15.4±1.1; p<0.001; n=8]. After 3 months of refeeding, there was no detectable difference in BW, blood pressure and heart rate between Ctrl and sFR-Refed groups. However, the renal artery blood flow was reduced by 13% [(mm/s): Ctrl, 255 ± 12 vs sFR-Refed, 199 ± 7.8; p<0.02; n=4-8 Glomeruli size was reduced [(mm): Ctrl, 399 ± 6.2 vs sFR-Refed, 383 ± 3.8; p<0.05; n=9] and renal AT1R mRNA expression was increased by 1.3-fold [(fold of Ctrl): Ctrl, 1.00 ± 0.060 vs sFR-Refed, 1.29 ± 0.040; p<0.005; n=8]. Conclusion: In summary, AT1Rs in the renal cortex are up-regulated under conditions in which kidney structure and function are impaired months after the sFR period has ended and BW is restored to normal levels. These findings suggest increased renal AT1R activity contributes to the long-term renal dysfunction observed in sFR-Refed rats. Further research is needed to understand how women who are subjected either voluntarily (e.g., crash diets) or involuntarily (e.g., very low food security) to periods of inadequate caloric intake could be at increased risk for developing renal disease later in life. AHA: 940246 (AS); IH 1R01HL119380 (KS) This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.